背景:先前的观察性研究表明,免疫介导的炎症性疾病(IMID)与牙周病之间存在双向关联。然而,关于IMID和牙周病的因果作用的证据仍然缺乏。因此,我们进行了一项双向双样本孟德尔随机化(MR)研究,以揭示IMID与牙周病之间的潜在遗传因果效应.
方法:采用双向双样本MR分析。10个IMID的数据来自FinnGen联盟进行的全基因组关联研究(GWAS)(范围为1023至36321例)和英国生物库(UKB)(范围为150至17574例)。此外,牙周疾病的GWAS数据来自FinnGen协会(87497例),UKB(458例),和基因生活方式相互作用在牙科终点(GLIDE)联盟(17,353例牙周炎)。随后,通过随机效应方差反加权分析因果关系,加权中位数,还有MR-Egger.使用CochraneQ检验进行敏感性分析,漏斗图,和Mr-Egger截距测试,以确保鲁棒性。最终,在不同数据库中进行复制分析和荟萃分析.
结果:系统性红斑狼疮(SLE)[IVW:OR=1.079(95%CI:1.032-1.128)和P<0.001],干燥综合征[IVW:OR=1.082(95%CI:1.012-1.157)和P=0.022]和甲状腺功能减退[IVW:OR=1.52(95%CI:1.13-2.04)和P=0.005]可能增加牙周病的风险。此外,牙周病可降低SLE[IVW:OR=0.8079(95%CI:0.6764-0.9650),P=0.019]和甲状腺功能亢进[IVW:OR=5.59*10-9(95%CI:1.43*10-15-2.18*10-2),P=0.014]的风险.荟萃分析表明SLE与牙周病风险增加之间存在因果关系:[OR=1.08(95%CI:1.03-1.13),P=0.0009]。没有重要证据表明其他IMID与牙周病之间存在双边因果关系。没有检测到异质性或多效性的显著估计。
结论:我们的研究证实了IMID与牙周病之间的遗传因果关系,从而揭示了IMID和牙周病潜在的新机制。这一发现有望促进临床医生和口腔医师之间的跨学科合作,以促进适当和精确的筛查。预防,以及IMID和牙周病的早期治疗。
BACKGROUND: Previous observational studies have shown a bidirectional association between immune-mediated inflammatory disorders (IMID) and periodontal disease. However, evidence regarding the causal role of IMID and periodontal disease is still lacking. Therefore, we conducted a bidirectional two-sample Mendelian randomization (MR) study to uncover the potential genetic causal effects between IMID and periodontal disease.
METHODS: Bidirectional two-sample MR analysis was employed. Data for ten IMIDs were sourced from genome-wide association studies (GWAS) conducted by the FinnGen Consortium (range from 1023 to 36321 cases) and UK Biobank (UKB) (range from 150 to 17574 cases). Furthermore, GWAS data for periodontal disease were obtained from the FinnGen Consortium (87497 cases), UKB (458 cases), and Gene Lifestyle Interactions in Dental Endpoints (GLIDE) consortium (17,353 periodontitis cases). Subsequently, the causal relationships were analyzed by random effects inverse variance weighting, weighted median, and MR-Egger. Sensitivity analyses were performed using the Cochrane Q test, funnel plot, and Mr-Egger intercept test to ensure robustness. Eventually, replication analysis and meta-analysis across different databases were carried out.
RESULTS: Systemic lupus erythematosus (SLE) [IVW: OR = 1.079 (95% CI: 1.032-1.128) and P < 0.001], Sjogren syndrome [IVW: OR = 1.082 (95% CI: 1.012-1.157) and P = 0.022] and hypothyroidism [IVW: OR = 1.52 (95% CI: 1.13-2.04) and P = 0.005] may increase the risk of periodontal disease. In addition, periodontal disease may reduce the risk of SLE [IVW: OR = 0.8079 (95% CI: 0.6764-0.9650) and P = 0.019] and hyperthyroidism [IVW: OR = 5.59*10-9 (95% CI: 1.43*10-15-2.18*10-2) and P = 0.014]. Meta-analysis indicated a causal correlation between SLE and an increased risk of periodontal disease: [OR = 1.08 (95% CI: 1.03-1.13), P = 0.0009]. No significant evidence suggests bilateral causal relationships between other IMIDs and periodontal disease. No significant estimation of heterogeneity or pleiotropy is detected.
CONCLUSIONS: Our study has confirmed a genetic causal relationship between IMIDs and periodontal disease, thereby unveiling novel potential mechanisms underlying IMIDs and periodontal disease. This discovery is promising in fostering interdisciplinary collaboration between clinicians and stomatologists to facilitate appropriate and precise screening, prevention, and early treatment of IMIDs and periodontal disease.